ERS Respiratory Channel

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Abstract

The activation of latent TGF-? by integrin ?_v?₆ is a well-known driver of fibrogenesis in idiopathic pulmonary fibrosis (IPF). Circulating levels of integrin beta-6 (ITGB6), the beta subunit of the integrin heterodimer ?_v?₆, were recently shown to be predictive of progression in patients with interstitial lung disease (Bowman, W.S. et al. Lancet Respir Med 2022; 10(6):593-602). In addition, we recently observed significantly reduced levels of circulating ITGB6 in patients with IPF receiving bexotegrast, a dual inhibitor of integrins ?_v?₆ and ?_v?₁ currently being evaluated in Phase 2 clinical trials for IPF (Lancaster, L. et al. ATS Int Conf May 2023). However, little is known about how ITGB6 concentrations in patients with IPF differ from those in healthy subjects.

Here we directly compared serum concentrations of ITGB6 in patients with IPF to healthy subjects by proximity extension assay (Olink). ITGB6 concentrations before and 3-12 months following lung transplant were also compared in a subset of patients.

Serum ITGB6 levels were significantly elevated by approximately 2.5-fold in patients with IPF compared to healthy controls (p < 0.0001; Fig 1A). Furthermore, serum ITGB6 concentrations were significantly reduced by an average of 36% in patients with IPF following lung transplant (p < 0.05; Fig1B). These data support further investigation of ITGB6 as a prognostic and therapeutic biomarker for IPF.

Abstract

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